Incidental findings from cancer next generation sequencing panels

Abstract Next-generation sequencing (NGS) technologies have facilitated multi-gene panel (MGP) testing to detect germline DNA variants in hereditary cancer patients. This sensitive technique can uncover unexpected, non-germline incidental findings indicative of mosaicism, clonal hematopoiesis (CH),...

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Autores principales:	Nika Maani, Karen Panabaker, Jeanna M. McCuaig, Kathleen Buckley, Kara Semotiuk, Kirsten M. Farncombe, Peter Ainsworth, Seema Panchal, Bekim Sadikovic, Susan Randall Armel, Hanxin Lin, Raymond H. Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Genetics QH426-470
Acceso en línea:	https://doaj.org/article/51d40d0aa8aa4187b039858a26fe2992
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spelling	oai:doaj.org-article:51d40d0aa8aa4187b039858a26fe29922021-12-02T16:26:27ZIncidental findings from cancer next generation sequencing panels10.1038/s41525-021-00224-62056-7944https://doaj.org/article/51d40d0aa8aa4187b039858a26fe29922021-07-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00224-6https://doaj.org/toc/2056-7944Abstract Next-generation sequencing (NGS) technologies have facilitated multi-gene panel (MGP) testing to detect germline DNA variants in hereditary cancer patients. This sensitive technique can uncover unexpected, non-germline incidental findings indicative of mosaicism, clonal hematopoiesis (CH), or hematologic malignancies. A retrospective chart review was conducted to identify cases of incidental findings from NGS-MGP testing. Inclusion criteria included: 1) multiple pathogenic variants in the same patient; 2) pathogenic variants at a low allele fraction; and/or 3) the presence of pathogenic variants not consistent with family history. Secondary tissue analysis, complete blood count (CBC) and medical record review were conducted to further delineate the etiology of the pathogenic variants. Of 6060 NGS-MGP tests, 24 cases fulfilling our inclusion criteria were identified. Pathogenic variants were detected in TP53, ATM, CHEK2, BRCA1 and APC. 18/24 (75.0%) patients were classified as CH, 3/24 (12.5%) as mosaic, 2/24 (8.3%) related to a hematologic malignancy, and 1/24 (4.2%) as true germline. We describe a case-specific workflow to identify and interpret the nature of incidental findings on NGS-MGP. This workflow will provide oncology and genetic clinics a practical guide for the management and counselling of patients with unexpected NGS-MGP findings.Nika MaaniKaren PanabakerJeanna M. McCuaigKathleen BuckleyKara SemotiukKirsten M. FarncombePeter AinsworthSeema PanchalBekim SadikovicSusan Randall ArmelHanxin LinRaymond H. KimNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Genetics QH426-470
spellingShingle	Medicine R Genetics QH426-470 Nika Maani Karen Panabaker Jeanna M. McCuaig Kathleen Buckley Kara Semotiuk Kirsten M. Farncombe Peter Ainsworth Seema Panchal Bekim Sadikovic Susan Randall Armel Hanxin Lin Raymond H. Kim Incidental findings from cancer next generation sequencing panels
description	Abstract Next-generation sequencing (NGS) technologies have facilitated multi-gene panel (MGP) testing to detect germline DNA variants in hereditary cancer patients. This sensitive technique can uncover unexpected, non-germline incidental findings indicative of mosaicism, clonal hematopoiesis (CH), or hematologic malignancies. A retrospective chart review was conducted to identify cases of incidental findings from NGS-MGP testing. Inclusion criteria included: 1) multiple pathogenic variants in the same patient; 2) pathogenic variants at a low allele fraction; and/or 3) the presence of pathogenic variants not consistent with family history. Secondary tissue analysis, complete blood count (CBC) and medical record review were conducted to further delineate the etiology of the pathogenic variants. Of 6060 NGS-MGP tests, 24 cases fulfilling our inclusion criteria were identified. Pathogenic variants were detected in TP53, ATM, CHEK2, BRCA1 and APC. 18/24 (75.0%) patients were classified as CH, 3/24 (12.5%) as mosaic, 2/24 (8.3%) related to a hematologic malignancy, and 1/24 (4.2%) as true germline. We describe a case-specific workflow to identify and interpret the nature of incidental findings on NGS-MGP. This workflow will provide oncology and genetic clinics a practical guide for the management and counselling of patients with unexpected NGS-MGP findings.
format	article
author	Nika Maani Karen Panabaker Jeanna M. McCuaig Kathleen Buckley Kara Semotiuk Kirsten M. Farncombe Peter Ainsworth Seema Panchal Bekim Sadikovic Susan Randall Armel Hanxin Lin Raymond H. Kim
author_facet	Nika Maani Karen Panabaker Jeanna M. McCuaig Kathleen Buckley Kara Semotiuk Kirsten M. Farncombe Peter Ainsworth Seema Panchal Bekim Sadikovic Susan Randall Armel Hanxin Lin Raymond H. Kim
author_sort	Nika Maani
title	Incidental findings from cancer next generation sequencing panels
title_short	Incidental findings from cancer next generation sequencing panels
title_full	Incidental findings from cancer next generation sequencing panels
title_fullStr	Incidental findings from cancer next generation sequencing panels
title_full_unstemmed	Incidental findings from cancer next generation sequencing panels
title_sort	incidental findings from cancer next generation sequencing panels
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/51d40d0aa8aa4187b039858a26fe2992
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Incidental findings from cancer next generation sequencing panels

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